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POLIO ENDGAME STRATEGY IN INDIA

CONSIDERATIONS AND WAY FORWARD

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WE FIRST THANK TO THE DEDICATED VOLUNTEERS, WITHOUT THEM POLIO ERADICATION IN INDIA IS NOT POSSIBLE

• Each national immunization day involved:

• 225,000,000 doses of polio vaccine• 172,000,000 children vaccinated

• 2,500,000 vaccinators• 2,000,000 vaccine carriers

• 155,000 supervisors

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Content● Introduction• Poliomyelitis disease

– Polio virus – Transmission, Pathogenecity– Clinical course – Diagnostic challenges– Complications

• Poliomyelitis vaccines– Oral Polio Vaccine (OPV)– Injectable Polio Vaccine (IPV)– Comparison between OPV & IPV

• Poliomyelitis eradication – Global scenario ( Past & Current )– Indian scenario ( Past & Current )

• End game strategy– What is the polio 'endgame'?– Why is the world now rethinking

the Polio Endgame?– What are the major elements of the 'New

Polio Endgame'?• Polio Endgame Strategy in India

Considerations and Way Forward

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Poliomyelitis crippled millions for centuries is on the verge of eradication!

● Etymology– Greek word: Polio (grey) + myelos (marrow)

• History– First described in 1789 in Europe – In next 100 years caused several

epidemics

• Impact of effective vaccines– Rapid decline in polio incidence – Only 3 countries are Polio endemic

• Global polio eradication in near future!

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Poliovirus is a highly pathogenic virus has 3 serotypes & there is no heterotypic immunity!

● Member of Picornaviridae family

– Enterovirus

– Small viruses with an RNA genome

– 3 serotypes (P1, P2 & P3)

♦ No heterotypic immunity

• Inhabitant of GIT & stable at acidic pH

• Rapidly inactivated by

– Heat / Formaldehyde / Chlorine / UV light

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Polio transmits via oro-fecal route!

• Humans are the only reservoirs

• Transmission– Fecal-oral route – No carriers

• No seasonality

• Communicability– Highly infectious for 7 - 10

days before & after onset

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Poliovirus can cause paralysis in 10 days!

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Behind every paralytic polio case there are 100 to 1000 poliovirus infections!

● 1 – 2% – Nonparalytic meningitis

• 4 – 8% – Abortive poliomyelitis

• 95% infections– Inapparent infections

• Incubation period– 6 – 20 days

• <1% – Flaccid paralysis

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Paralysis is the major complication of poliomyelitis!

• Complications – Spinal polio

• 80% of paralytic cases• Asymmetric paralysis of legs

– Bulbar polio• 2% of paralytic cases• Muscle weakness

– Bulbospinal polio• 18% of cases• Mixed morbidity

• Case Fatality Rate– 2 – 5% (in children )– 15 – 30% (in adults)

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Diagnosing poliomyelitis is a clinical challenge, as many diseases & conditions cause AFP!

• Differential diagnosis of acute flaccid paralysis– Commonest

• Gullian-Barre syndrome• Transverse myelitis

– Infections• Viral - Enteroviruses & other viruses

– Toxins• Bacterial (e. g. Botulinm, Tetanus) & fungal• Venoms (e. g. Ticks, spider, beetle, wasp &

snake)• Organic chemicals & pesticides

– Metabolic disorders• Hypokalemia & Hypophosphatemia

– Traumatic neuritis (Post injection)

In 1988 the World Health Assembly passed a resolution to eradicate polio, launching the Global Polio Eradication Initiative

In 1995,In India, 87 million children were vaccinated.

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Global Status 1988

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GLOBAL STATUS 2004

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*2012 : 299 cases (as of 9th Oct, 2012)

7 countries ( Endemic-3, Importation-4 )

% cases decrease: > 99%

1988 : 350,000 cases> 125

countries

Polio Eradication : 1988 - 2012YEAR NO.OF POLIO

CASES

1988 350000

1993 1925

1998 1934

1999 1186

2000 265

2001 211

2002 1919

2003 784

2004 1556

2005 1831

2006 2022

2007 1387

2008 1732

2009 1783

2010 1413

2011 716

2012* 299

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0

250

500

750

1000

1250

1500

1750

2000

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008*

SAW SEE Polio cases

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Rolling Towards the Success story

* as of 13th October 2012

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HOPE THIS ISLAST POLIO CASE

Baby Rukhsar, Howrah

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So, India appears on track to Stop Polio

Finally, India achieved interruption of transmission for Nearly 2 Years

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Polio cases in the world in 2012

                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        

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What has been the cost towards this achievement…???

International investment of over US$ 8 billion

MoH: India has spent INR1200 crores towards Polio control so far

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It took 75 years of scientific efforts for eliminating polio from most part of the world!

Polio Virus

Albert B. Sabin Created first oral polio vaccine

Jonas Salkcreated first injectable

polio vaccine

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In 1952 Prof. Salk created world’s first IPV!

• Tissue Culture Era (1950 – 1951)• Cultivation in non-nervous tissue • Plaque technique to improve yield

• Inactivated vaccines– 1952 - 1953

• Prof. Salk – Safety & immunogenicity in animals & humans

– 1954• Vaccine field trial by University of Michigan, US• 1,829,916 children enrolled (US, Canada & Finland)

– 1955• Trial results published – Safe & 70% effective

– 6 manufacturers permitted licenses

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– 1952 ♦ Prof. Sabin identified characteristics of

candidate virus for OPV♦ Developed neurovirulence model in

monkey – 1957 - WHO recommended field trials

– 1958 - Singapore – 200,000 children vaccinated

– 1959 - USSR – 1,500,000 children vaccinated

– 1960 - > 100,000,000 children vaccinated

In 1954 Prof. Sabin created world’s first OPV!

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OPV protects the community by conferring high level of herd immunity!

● Monodose (0.5 mL) in a plastic dispenser

• Live attenuated strains of 3 serotypes (10:1:3)• Viruses replicate in intestine, lymph tissues

• Viruses excreted in stool up to 6 wks• Herd immunity effect

– Persons coming in contact with fecal material of a vaccinated child get protected

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Though OPV is highly immunogenic vaccine, it is a “hit / miss” vaccine, with associated risk of VAPP!

● Immunogenicity & vaccine efficacy– Highly immunogenic

♦ 1 dose - 50% recipients♦ 3 doses - 95% recipients

– Produces intestinal immunity• Prevent infection with wild virus

• Drawbacks– “Hit / Miss” vaccine!– Vaccine Associated Paralytic

Poliomyelitis

– Provides lifelong immunity

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Risk of VAPP with OPV is rare, but……………………immunodeficient children have 7000 times higher risk!

– Risk of VAPP• <1/1,000,000 )

– Type of virus• Type 3 (most cases in vaccinees) & Type 2 (most cases in

contacts)

• Vaccine Associated Paralytic Poliomyelitis (VAPP)– Accounts for 95% of all cases of paralytic poliomyelitis

– At risk population• Persons of > 18 years • Immunodeficient children (e.g. malnutrition)

– Cause♦ Mutation / reversion of virus (revertant) to more neurotropic form

– Paralysis identical to that caused by wild virus

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• Vaccine Associated Paralytic Poliomyelitis (VAPP), • The global burden is estimated at 250–500 cases annually• In 2000 in Hispaniola when 21 children were

paralysed, first cVDPV outbreak was identified• Long term Carriers of VDPVs identified among

immunodeficient (iVDPVs) reseed in general population

• In the Philippines in 2001 cVDPV outbreak in 3 and in Madagascar in 2002, 4 children.

• Retrospective analyses documented cVDPV circulation in Egypt 1988 -1993 30 cases

• So, they all have the potential to cause Outbreaks in underimmunized

populations

Risks of OPV

VDPV

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cVDPV Globally

http://www.polioeradication.org/

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Injectable Polio Vaccine

● IPV (Salk) 1955●Enhanced IPV 1970’s

available since 1988 in US used worldwide.

●Highly immunogenic >90% protection 2 doses

Murdin AD, Vaccine 1996;14.,

Robertson, Lancet 1998;352

●98-100%seroprotection all 3 serotypes Vidor E,Ped.Infec

Dis.1997;16

● Ideal vaccine for individual protection Thacker & Shendurnikar,IJP 2003;70

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Risk of VAPP can be eliminated by administrating IPV prior to OPV!

● Control of VAPP (Learning from US scenario)

– 1996♦ ACIP recommended IPV followed by OPV

• Production of humoral immunity against polio vaccine virus

– 1998• Fewer cases of VAPP

– 2000• Exclusive IPV vaccination form 2000

– Elimination of shedding of live vaccine virus

– Elimination of VAPP

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IPV administration is safe during minor illnesses, including diarrhoea & URTI!

●Contraindication– Hypersensitivity to any vaccine component

• Special precautions– Severe acute illness

• Breastfeeding – No interference

• Minor illnesses– Can be administered to a child with diarrhea– Minor illness is not contraindications

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Most IPVs use vero cell substrate for virus growth & the virus is inactivated by formaldehyde!

● Single dose prefilled syringe

● Administered by IM injection

• Contains all 3 serotypes of virus

• Inactivated with formaldehyde

• 2-phenoxyethanol as preservative

• Traces of neomycin, streptomycin & polymyxin B

Manufacturer CountryCell

substrateNovartis Italy Vero

France VeroCanada & MRC - 5

GSK Belgium VeroNational Biological Laboratory

Sweden Vero

Rhesus Monkey Kidney& Vero

Sanofi Pasteur

Netherlands Vero

Statens Serum Institute

Denmark

Netherlands Vaccine Institute

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What is the polio 'endgame'?The endgame: addressing risks due to the oral polio vaccine (OPV) after eradication

●Vaccine-Associated Paralytic Poliomyelitis (VAPP): very rare adverse event.

●Outbreaks of circulating vaccine-derived poliovirus (cVDPV): very rare event; occurs when vaccine virus regains ability to paralyze and circulate.

'After interruption of wild poliovirus, continued use of OPV would compromise the goal of a polio-free world.

Expert Consultation on Vaccine-derivedPolioviruses (VDPVs), Sept 2003, Geneva

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VDPV elimination & validation

Wild virus eradication

World Health Assembly (2008)

Post-OPV surveillance

Certification & containment

Evolution of the 'Post-Eradication' Timeline

0 2 4 6 8 10 12 Years

Wild virus eradication

Certification Commission '95

Certification

Last polio case OPV cessation

The 'endgame' period

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Why is the world now rethinkingthe Polio Endgame?

Recent developments allow a major 'rethink' of the endgame

• New bivalent vaccine (bOPV) outperforms trivalent OPV.

• New diagnostics show type 2 OPV is the main problem.

• New, very low cost 'IPV options' can allow all countries to continue type 2 immunization if they want/need to.

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Current Understanding of cVDPVs

circulating Vaccine-Derived Poliovirus Outbreaks (cVDPVs) 2000-2010

Type 2 (450 cases)

Type 1 (79 cases)

Type 3 (9 cases)

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Affordable IPV options in the short-term,

Full-dose

$3

$0.6

Current price

(low volume)

< $0.3

IPV price

($ per dose)

** assumes full dose price of < US$1.5/dose at high volume

1/5th of 1 dose of IPV could be very affordable (<$0.5/dose)

1/5th fractional dose

Expected price

(high volume**)

1/5th of 1 dose of IPV can induce a response in >90% of children

0

10

20

30

40

50

60

70

80

90

100

P1 P2 P3

Response* after 1 dose

(%, intradermal IPV, Cuba)

* includes seroconversion & priming

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What are the major elements of the 'New Polio Endgame'?

New Polio Endgame: Guiding Principles

• phased removal of Sabin/OPV viruses, beginning with highest-risk (type 2).

• elimination of type 2 in parallel by switching from tOPV to bOPV for routine EPI & campaigns.

• introduction of 1 IPV dose to boost immunity prior to a tOPV-bOPV switch & provide type 2 'priming'.

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New 'Endgame' strategy: parallel risk management

0 2 4 6 8 10 12

Years

Last wild polio case trivalent OPV cessation

VDPV elimination & validation

Wild virus eradication

Sequential risk management

Post-OPV surveillance

Certification & containment

VDPV2 elimination & validation

Post-OPV surveillance

Wild virus eradication

Parallel risk management

Certification & containment

OPV2 cessation& IPV introduction

bivalent OPV 1&3 (bOPV) cessation

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Advantages of the New Approach

• accelerate type 1 & 3 eradication (with bOPV)

• address >90% of VDPV risk while surveillance & response capacity is optimized

• substantially shorten the post-eradication phase

• boost routine immunization coverage (i.e. IPV at DPT3)

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Polio Endgame Strategy in IndiaConsiderations and Way Forward

● No WPV2 in India since 1999

● tOPV used in RI and during NIDs

● bOPV used in most SNIDs since Jan 2010

● Areas and populations with low routine immunization coverage

● All cVDPVs in India due to type 2 in setting of low immunity to type 2

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Last wild poliovirus cases by type, India

WPV2 24/10/1999

Aligarh (UP)

WPV1 13/01/2011

Howrah (WB)

WPV3 22/10/2010Pakur (JH)

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A

Current pattern of vaccine use-India

●tOPV– EPI schedule: 6,10,14 wks

Birth dose for institutional births – SIAs: 2 NIDs with tOPV each year

●bOPV– Introduced in Jan 2010– Used extensively during SNIDs in high

risk states/ areas

70.4%

<6060 - 7070 - 80>= 80

AssessedtOPV3 coverageby CES 2009

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cVDPV cases, India 2009-2011

•cVDPV cases detected in 2009-10

•100% due to type 2

DistrictType 2

2009 2010 2011

Badaun 3 0 0

Bulandshahar 2 0 0

Ghaziabad 0 1 0

Meerut 2 0 0

Moradabad 2 0 0

Pilibhit 4 0 0

Shahjahanpur 2 1 0

Total 15 2 0

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Low seroprevalence against poliovirus type 2Results from different serosurveys

Moradabad Nov 2007(N=121)

AFP cases UPNov 08 –

mid 09(169)

Moradabad May 2009(N=534)

UP & BiharAug 2010(N=1280)

UP & BiharAug 2011(N=1246)

Age 6-7 mo 6-11 mo 6-7 mo 6-7 mo 6-11 mo

Type 1 78% 96.5% 99% 98% 98.5%

Type 2 56% 33.7% 75% 65% 85%

Type 3 69% 42.6% 49% 77% 88.2%

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0

1

2

3

4

5

6

7

8

9

10

J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A S O N D

cVDPV type 2

Uttar Pradesh

2009 2010 2011

Nu

mb

er

of

ca

se

s

c VDPV type 2

tOPV

< 25%25 to 50%50 to 75%>= 75%

District.shp0 - 24.925 - 49.950 - 74.975 - 100

State.shp

200 0 200 400 Miles

N

EW

S

View1

tOPVsNID

tOPVNID

tOPVsNID

tOPVNID

Evaluated OPV3 coverage by district – DLHS 3 (2007-08) and cVDPVs

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State Type 1 Type 2

Assam 1Bihar 3Karnataka 1Madhya Pradesh 1Rajasthan 1Uttar Pradesh 4West Bengal 1

Total 1 11

iVDPV & aVDPV cases, India 2009 to 2012*

*: data as on 10 March 2012

iVDPV aVDPV

State Type 1 Type 2 Type 3

Chhattisgarh 1Punjab 1Tamil Nadu 1Uttar Pradesh 1Odisha 1

Total 1 3 1

ambiguous VDPV (aVDPV): origin uncertain e.g. single isolate from single AFP case, non-immunodeficient person

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tOPV-bOPV switch in India? Considerations

● Pre-switch increase in type 2 immunity● Rapidly improve routine immunization coverage● Use of IPV in conjunction with bOPV/tOPV to reduce risk of

emergence and consequences of cVDPV● Availability of vaccines

– IPV availability for use in routine immunization– bOPV availability for routine immunization and SIAs

● Management of post-switch risks of type 2 VDPVs● cVDPV type 2 circulation stopped everywhere & switch

synchronised globally

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NID NID

0Jan Mar May Jul Sep Nov Jan Mar May Jul Sep Nov Jan Mar May Jul Sep Nov Jan Mar May

Polio Endgame Strategy-India, Possible Way Forward

2011 2012 2013 2014

Last WPV case

Polio certification

IPV NID NID

tOPV NID

Post-switch Sabin type 2 risk mgt.

tOPV-bOPV switch

NID NID NID NID

Certification standard surveillance, improved RI coverage

PQ/ licensing, stockpile

Modelling, Research, Development

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ConclusionsWhile the past cannot be re-enacted, the future can certainly be redesignedSequential IPV/OPV schedules considered 1st phase transition towards all IPV schedule in Routine Immunzation.The program should attend TO COUNTRY SPECIFIC NEEDSAnd Not get overawed by Global needsHope this Debate will not only generate a Nation wide Debate but also create the Need in the best interest of country.

Ultimately success of the whole initiative will depend on steps being taken now to improve the economics of IPV. V Vashishtha RTC Series 2010(24) RSF India

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HOPE THIS IS THE HISTORICAL LAST POLIO CASE OF INDIA

THANK YOU